Valproic acid or valproate (VpA) is an anticonvulsive drug used for treatments of epilepsy, bipolar disorder, and migraine headaches. VpA is also an epigenetic modulator, inhibiting histone deacetylase, and it has been subjected to clinical study for cancer treatment. During the investigation of VpA on a metabolite profile in a fungus, we found that VPA has significant effects on the production of some fatty acids. Further exploration of VPA on fatty acid profiles of microorganisms, fungi, yeast, and bacteria, as well as representative gut microbiome, revealed that VpA could enhance or reduce the production of some fatty acids. VpA was found to induce the production of trans-9-elaidic acid, a fatty acid that was previously reported to have cellular effects in human macrophages. VPA could also inhibit the production of some polyketides produced by a model fungus. the present work suggests that the induction or inhibition of fatty acid biosynthesis by VPA (100 µM) in gut microbiome could give effects to patients treated with VPA because high doses of VPA oral administration (up to 600 mg to 900 mg) are used by patients; the concentration of VPA in the human gut may reach a concentration of 100 µM, which may give effects to gut microorganisms. Valproic acid (VPA) or valproate, an anticonvulsive drug, has been used as drug for the treatment of epilepsy, bipolar disorder, and for the prevention of migraine headaches. VPA has side effects, for example, hepatic steatogenesis in rats 1 , and negative influence on hepatic carbohydrate and lipid metabolism 2. There were a number of fatal cases of hyperammonemia for patients treated with VPA 3. In mitochondria, VPA undergoes fatty acid β-oxidation pathway, causing toxicity due to interference with mitochondrial β-oxidation, and many serious inborn errors of metabolism are caused by VPA treatment 4. VPA interferes with carnitine palmitoyl-transferase I, a key enzyme in mitochondrial fatty acid β-oxidation, and thus inducing hepatotoxicity and weight gain for patients under VPA therapy 5. VPA could inhibit N-acetyl glutamate synthetase, and thus inhibiting urea synthesis 6,7. VPA was found to induce abnormal autism-like behaviors in mice 8. Recently, a number of research groups paid attention on the risk of VPA on autism spectrum disorders 9-14. The discovery that VPA is an inhibitor of histone deacetylase, a promising anticancer drug target, has stimulated the scientific community worldwide to investigate the detailed mechanisms of VPA in various aspects 15,16. Recently, drug repurposing of VPA has been intensively explored for the treatment of various diseases, for example, the treatment of breast cancer 17 , colon cancer associated with diabetes mellitus 18 , diffuse intrinsic pontine glioma 19 , high-fat diet-induced hypertension 20 ,

The antibody responses to new SARS-CoV-2 variants that occur in different populations remain unclear. In this study, we recruited 60 participants, including COVID-19 patients and CoronaVac-vaccinated individuals, in Thailand and determined the dynamic levels of the IgG, IgA, IgM, and IgG subclasses of antibodies against the spike protein (S) of four SARS-CoV-2 strains.

Valproic acid or valproate (VPA) is a drug for the treatment of epilepsy, bipolar disorder, migraine headaches and neuropathic pain. Unfortunately, VPA has many side effects. In this work, it was found that productions of some fatty acids were significantly affected by VPA at the concentration of 100 μM. Further exploration of VPA on fatty acid production in microorganisms including fungi, yeast, and bacteria, as well as representative gut microbiome. This work showed that VPA could enhance, reduce or completely inhibit the production of some fatty acids. VPA could induce the production of trans-9-elaidic acid that was previously found to have cellular effects in human macrophages. Moreover, VPA was found to inhibit the production of some polyketides produced by a model fungus. This work also investigated bioactive compounds from a plant, Feroniella lucida (Scheff.) Swingle and a termite-associated fungus ISFB10. Candicine (7) and candicine derivative (8) were isolated from spine part of F. lucida. Compound 8 exhibited weak cancer chemoprevention activity in the xanthine oxidase assay (XXO) with an IC50 value of 473.8±13.4 μM. Roridin A (9) and verrucarin A (10) were isolated from the termite-associated fungus ISFB10. Compounds 9 exhibited strong cytotoxic activities toward HuCCA-1, A549, MOLT-3 and HepG2 cancer cell lines with IC50 values of 0.016±0.0007, 0.0055±0.0001, 0.005±0.0003 and 0.024±0.002 µM, respectively. Compounds 10 also exhibited strong cytotoxic activities toward HuCCA-1, A549, MOLT-3 and HepG2 cancer cell lines with IC50 values of 0.014±0.0005, 0.0047±0.0005, 0.008±0.0002 and 0.019±0.001µM, respectively. Unfortunately, compounds 9 and 10 were also exhibited strong cytotoxic activity toward normal cell line MRC-5 with IC50 values of 0.038±0.006 and 0.012±0.0004, respectively.